A Confirmatory Study of Fentanyl in Participants With Pos... | NCT01008553

ID	Type	Description	Link
JNS020QD-JPN-N02

Label	Type	Description	Intervention Names
Fentanyl (Titration period)	Experimental	One-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) containing fentanyl (JNS020QD) applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 microgram per hour (mcg/hr) for at least first 2 days, which will be increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and visual analog scale (VAS) score of the participants. The dose will be increased up to maximum of 50 mcg/hr. The treatment will continue for 10-29 days and then the eligible participants from this group will be randomly assigned to either of the two groups in the double-blind period.	Drug: Fentanyl
Fentanyl (Double-blind period)	Experimental	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, will be administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which will be same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment will be continued for 12 weeks.	Drug: Fentanyl
Placebo (Double-blind period)	Placebo Comparator	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, will be administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) will be gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo will be gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment will continue for 12 weeks.

Name	Type	Description	Arm Group Labels	Other Names
Fentanyl	Drug	One-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm and thigh and replaced every day.	Fentanyl (Double-blind period)

Measure	Description	Time Frame
Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy	Time from start of double-blind (researchers and participants were unaware of the treatment) period to withdrawal because of insufficient analgesic efficacy based on any of the pre-defined discontinuation criteria was noted.	Day 1 up to Day 85 (double-blind period) and Day 92 (discontinuation of the study)

Measure	Description	Time Frame
Pain Visual Analog Scale (VAS) Score - Titration Period	The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a "100-millimeter (mm) VAS scale" by drawing a slash. The left margin (0 mm) was considered "No pain at all", and the right margin (100 mm) was considered "Severer pain than this is inconceivable". The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of Screening period and during 3 days before the end of titration period was reported.

Name	Affiliation	Role
Janssen Pharmaceutical K.K., Japan Clinical Trial	Janssen Pharmaceutical K.K.	Study Director

PubMed Identifier	Type	Citation	Retractions
26359327	Derived	Arai T, Kashimoto Y, Ukyo Y, Tominaga Y, Imanaka K. Two placebo-controlled, randomized withdrawal studies to evaluate the fentanyl 1 day patch in opioid-naive patients with chronic pain. Curr Med Res Opin. 2015 Dec;31(12):2207-18. doi: 10.1185/03007995.2015.1092127. Epub 2015 Oct 19.

ID	Title	Description
FG000	Fentanyl (Titration Period)	One-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) containing fentanyl (JNS020QD) applied to chest, abdomen, upper arm or thigh and replaced every day, starting at the dose of 12.5 microgram per hour (mcg/hr) for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and visual analog scale (VAS) of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy

Time from start of double-blind (researchers and participants were unaware of the treatment) period to withdrawal because of insufficient analgesic efficacy based on any of the pre-defined discontinuation criteria was noted.

Full analysis set (FAS) population included all the randomly assigned participants with the exception of participants with pre-defined criteria.

Posted

Median

95% Confidence Interval

Days

Day 1 up to Day 85 (double-blind period) and Day 92 (discontinuation of the study)

ID	Title	Description
OG000	Fentanyl (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.
OG001	Placebo (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.

Units	Counts
Participants	OG00084 OG00179

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)The data was not estimable due to the high number of participants censored for this outcome measure. OG00145.0(16.0 to NA)The upper limit of 95% confidence interval was not estimable due to the high number of participants censored for this outcome measure.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.0003													No	Superiority or Other

Secondary

Pain Visual Analog Scale (VAS) Score - Titration Period

The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a "100-millimeter (mm) VAS scale" by drawing a slash. The left margin (0 mm) was considered "No pain at all", and the right margin (100 mm) was considered "Severer pain than this is inconceivable". The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of Screening period and during 3 days before the end of titration period was reported.

Full analysis set in Period 1 (FAS1) population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.

Posted

Mean

Standard Deviation

Day 12-14 (Screening period) and Day 27-29 (Titration period)

ID	Title	Description
OG000	Fentanyl (Titration Period)	One-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) containing fentanyl (JNS020QD) applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 microgram per hour (mcg/hr) for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and visual analog scale (VAS) score of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period.

Secondary

Pain Visual Analog Scale (VAS) Score - Double-Blind Period

The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a "100-millimeter (mm) VAS scale" by drawing a slash. The left margin (0 mm) was considered "No pain at all", and the right margin (100 mm) was considered "Severer pain than this is inconceivable". The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of titration period and during 3 days before the end of double-blind period was reported.

The FAS population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.

Posted

Mean

Standard Deviation

Day 27-29 (Titration period) and Day 83-85 (double-blind period)

ID	Title	Description
OG000	Fentanyl (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.
OG001	Placebo (Double-blind Period)

Secondary

Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period

The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: "Extremely satisfied", "Satisfied", "Neither satisfied nor dissatisfied", "Dissatisfied" and "Dissatisfied very much". The results were reported as Category 1 = At least "Neither satisfied nor dissatisfied", which included participants with general evaluation of "Extremely satisfied" to "Neither satisfied nor dissatisfied", and Category 2 = At least "Satisfied", which included participants with general evaluation of "Extremely satisfied" to "Satisfied".

The FAS1 population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.

Posted

Number

Participants

Day 1 and 29 or final evaluation (Titration period)

ID	Title	Description
OG000	Fentanyl (Titration Period)	One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 mcg/hr for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and VAS score of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period.

Secondary

Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period

Posted

Number

Participants

Day 1 and 85 or final evaluation (double-blind period)

ID	Title	Description
OG000	Fentanyl (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.
OG001	Placebo (Double-blind Period)

Secondary

Number of Doses of Rescue Treatment Per Day - Titration Period

If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary.

Posted

Mean

Standard Deviation

Treatments per day

Day 1 and 29 or final evaluation (Titration period)

ID	Title	Description
OG000	Fentanyl (Titration Period)	One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 mcg/hr for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and VAS score of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period.

Secondary

Number of Doses of Rescue Treatment Per Day - Double-Blind Period

Posted

Mean

Standard Deviation

Treatments per day

Day 1 and 85 or final evaluation (double-blind period)

ID	Title	Description
OG000	Fentanyl (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.
OG001	Placebo (Double-blind Period)

Secondary

Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period

The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions [questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 [questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)]). Total score ranges from 0 to 10 with higher values indicating more pain.

Posted

Mean

Standard Deviation

Units on a scale

Day 1 and 29 or final evaluation (Titration period)

ID	Title	Description
OG000	Fentanyl (Titration Period)	One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 mcg/hr for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and VAS score of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period.

Secondary

Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period

Posted

Mean

Standard Deviation

Units on a scale

Day 1 and 85 or final evaluation (double-blind period)

ID	Title	Description
OG000	Fentanyl (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.
OG001	Placebo (Double-blind Period)

Secondary

Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Titration Period

The SF-36v2 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state.

Posted

Mean

Standard Deviation

Units on a scale

Day 1 and 29 or final evaluation (Titration period)

ID	Title	Description
OG000	Fentanyl (Titration Period)	One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 mcg/hr for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and VAS score of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period.

Secondary

Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period

Posted

Mean

Standard Deviation

Units on a scale

Day 1 and 85 or final evaluation (double-blind period)

ID	Title	Description
OG000	Fentanyl (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.
OG001

Secondary

Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period

Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective.

The FAS1 population included all the randomly assigned participants with the exception of participants with pre-defined criteria.

Posted

Number

Participants

Day 29 or final evaluation (Titration period)

ID	Title	Description
OG000	Fentanyl (Titration Period)	One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 mcg/hr for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and VAS score of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period.

Units	Counts
Participants	OG000

Secondary

Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period

Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective.

Posted

Number

Participants

Day 1 and 85 or final evaluation (double-blind period)

ID	Title	Description
OG000	Fentanyl (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.
OG001	Placebo (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG00012 affected258 at risk EG0015 affected84 at risk EG0026 affected79 at risk
Cystitis	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Gastroenteritis	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Herpes simplex	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Hordeolum	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Pharyngitis	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Seasonal allergy	Immune system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00017 affected258 at risk EG0017 affected84 at risk EG0024 affected79 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Delirium	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0007 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Insomnia	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0007 affected258 at risk EG0013 affected84 at risk EG0021 affected79 at risk
Disorientation	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Hallucination	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Hallucination, visual	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Middle insomnia	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Nightmare	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Restlessness	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Sleep disorder	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Abulia	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Somnolence	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG000118 affected258 at risk EG00112 affected84 at risk EG0025 affected79 at risk
Dizziness	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00052 affected258 at risk EG0016 affected84 at risk EG0023 affected79 at risk
Headache	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0006 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Tremor	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0004 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Amnesia	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Dysarthria	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Cerebral infarction	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Disturbance in attention	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Dyslalia	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Hypoaesthesia	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Memory impairment	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Parkinsonism	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Parkinsonian gait	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Photophobia	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Cataract	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Iritis	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Uveitis	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Visual impairment	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Vitreous floaters	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Ear discomfort	Ear and labyrinth disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Palpitations	Cardiac disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0004 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Tachycardia	Cardiac disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Hypertension	Vascular disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Oropharyngeal discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG000124 affected258 at risk EG00112 affected84 at risk EG00210 affected79 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG000103 affected258 at risk EG00112 affected84 at risk EG00210 affected79 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00025 affected258 at risk EG0015 affected84 at risk EG0021 affected79 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00017 affected258 at risk EG0015 affected84 at risk EG0029 affected79 at risk
Stomatitis	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0004 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Gastritis	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Gingivitis	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Cheilitis	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Dysphagia	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Gingival pain	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Oral discomfort	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0012 affected84 at risk EG0021 affected79 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00013 affected258 at risk EG0015 affected84 at risk EG0020 affected79 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00010 affected258 at risk EG0012 affected84 at risk EG0022 affected79 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0008 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0008 affected258 at risk EG0013 affected84 at risk EG0021 affected79 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0007 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0004 affected258 at risk EG0010 affected84 at risk EG0022 affected79 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Heat rash	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0010 affected84 at risk EG0022 affected79 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0022 affected79 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0011 affected84 at risk EG0022 affected79 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Dysuria	Renal and urinary disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0004 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Urinary retention	Renal and urinary disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Pollakiuria	Renal and urinary disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Application site pruritus	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00015 affected258 at risk EG0012 affected84 at risk EG0021 affected79 at risk
Thirst	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00015 affected258 at risk EG0013 affected84 at risk EG0021 affected79 at risk
Malaise	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG00012 affected258 at risk EG0017 affected84 at risk EG0024 affected79 at risk
Application site erythema	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0008 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Pyrexia	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0008 affected258 at risk EG0011 affected84 at risk EG0022 affected79 at risk
Application site dermatitis	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0004 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Feeling abnormal	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0004 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Oedema peripheral	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0004 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Application site rash	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Drug withdrawal syndrome	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Oedema	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Chest pain	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Chills	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Pain	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Discomfort	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Puncture site pain	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Blood pressure increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0008 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Aspartate aminotransferase increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Blood urea increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0003 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Alanine aminotransferase increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Blood creatinine increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Weight decreased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Blood potassium increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Blood pressure decreased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Haemoglobin decreased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Liver function test abnormal	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Monocyte count increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Red blood cell count decreased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Weight increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Lymphocyte percentage decreased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Protein urine present	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0002 affected258 at risk EG0013 affected84 at risk EG0022 affected79 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0010 affected84 at risk EG0020 affected79 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Wound	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0001 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Anal candidiasis	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Onychomycosis	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Pneumonia	Infections and infestations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Gout	Metabolism and nutrition disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Anxiety	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Apathy	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Depression	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Euphoric mood	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Depressive symptom	Psychiatric disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Loss of consciousness	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Autonomic nervous system imbalance	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Dyskinesia	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Extrapyramidal disorder	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Migraine	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Speech disorder	Nervous system disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Conjunctivitis allergic	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Dry eye	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Keratitis	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Vision blurred	Eye disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Atrial fibrillation	Cardiac disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Bundle branch block right	Cardiac disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Haematoma	Vascular disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Upper respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Salivary hypersecretion	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0012 affected84 at risk EG0021 affected79 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0024 affected79 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Sweat gland disorder	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Haematuria	Renal and urinary disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0021 affected79 at risk
Renal impairment	Renal and urinary disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0022 affected79 at risk
Irritability	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Chest discomfort	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Drug interaction	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Loss of control of legs	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Puncture site reaction	General disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Eosinophil count increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0022 affected79 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Blood glucose increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Electrocardiogram abnormal	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Glucose urine present	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Neutrophil count increased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Electrocardiogram ST-T segment abnormal	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Urine output decreased	Investigations	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Joint sprain	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0012 affected84 at risk EG0020 affected79 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0010 affected84 at risk EG0021 affected79 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA Version 13.0	Non-systematic Assessment	EG0000 affected258 at risk EG0011 affected84 at risk EG0020 affected79 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Aichi			Japan

ID	Term
D051474	Neuralgia, Postherpetic
D020918	Complex Regional Pain Syndromes
D010149	Pain, Postoperative

ID	Term
D009437	Neuralgia
D010523	Peripheral Nervous System Diseases
D009468	Neuromuscular Diseases
D009422	Nervous System Diseases
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D001342	Autonomic Nervous System Diseases
D011183	Postoperative Complications
D010335	Pathologic Processes

ID	Term
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Fentanyl (Titration Period)	One-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) containing fentanyl (JNS020QD) applied to chest, abdomen, upper arm or thigh and replaced every day, starting at the dose of 12.5 microgram per hour (mcg/hr) for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and visual analog scale (VAS) of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period.	13	258	231	258
EG001	Fentanyl (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm or thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.	8	84	71	84
EG002	Placebo (Double-blind Period)	Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm or thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks.	4	79	56	79